PROJECT SUMMARY. Polycystic ovary syndrome (PCOS) is a complex endocrine disorder whose symptoms and co-morbidities have far-reaching implications for the health and well-being of women across the lifespan. While the name of this condition implies a specific abnormality in ovarian morphology, significant controversy surrounds the relevance of polycystic ovaries (PCO) to the diagnosis and clinical spectrum of PCOS. A high prevalence of PCO has been reported in healthy women with normal ovulatory function. This has called into question the specificity of PCO to the condition of PCOS, as well as its ability to inform risk for or progression of the disease, and response to treatment. We recently showed that longstanding sonographic criteria for PCO are obsolete owing to the significant improvements in imaging technology that have occurred in the 12 years since their proposal. Despite momentum toward adopting new criteria for PCO, these most recent recommendations are limited. They do not account for the known impact of age or potential influence of adiposity on ovarian morphology. Nor do they provide insight into the etiology or degree of disordered folliculogenesis in PCOS. The following proposal aims to refine the sonographic definition of PCO by using state-of-the-art ultrasound imaging technology and standardized approaches to contrast ovarian morphology across a broad spectrum of women with PCOS. We believe that the basis for defining PCO on ultrasonography should reflect an understanding of antral follicle development in this condition. The central hypothesis proposed is that PCO morphology on ultrasonography captures unique disruptions in antral follicle development that can inform both clinical and functional outcomes in women with PCOS. The specific aims of this project are to: (1) develop ultrasonographic criteria for PCO that maintain specificity for PCOS across adulthood and body habitus; (2) determine the potential of ovarian morphology to inform the clinical presentation of PCOS across adulthood; and (3) develop a model of antral follicle development in PCOS that accounts for the unique aspects of PCO morphology and their ability to predict the ovulatory response to dietary intervention. By refining and expanding the role of ultrasonography in the clinical evaluation of PCOS, this research will reduce the misdiagnoses of PCOS, promote the early identification of patients at risk for concurrent comorbidities, and usher new approaches for tailored interventions that account for the spectrum of disordered folliculogenesis characteristic to this condition. These efforts to clarify the relevance of PCO morphology are consistent with prioritized areas of research identified by the recent NIH Evidence-Based Methodology Workshop on PCOS.